Journal
BIOLOGICAL PSYCHIATRY
Volume 88, Issue 2, Pages 197-207Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2019.12.027
Keywords
fMRI; Functional connectivity; Global brain connectivity; Psilocybin; Receptor gene expression; Serotonin
Categories
Funding
- Heffter Research Institute [1190420]
- Swiss Neuromatrix Foundation [2016-0111]
- Swiss National Science Foundation under the framework of Neuron Cofund [01EW1908]
- Slovenian Research Agency (ARRS) [J7-8275, J7-6829, P3-0338]
- SFARI Pilot Award
- National Institutes of Health [1U01MH121766, R01MH112746, 5R01MH112189, 5R01MH108590, 5P50AA012870]
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BACKGROUND: The use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans. METHODS: We conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and 0.2 mg/kg of psilocybin orally on 2 different test days. Participants underwent magnetic resonance imaging at 3 time points between administration and peak effects: 20 minutes, 40 minutes, and 70 minutes after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared with cortical gene expression maps. RESULTS: Psilocybin reduced associative, but concurrently increased sensory, brain-wide connectivity. This pattern emerged over time from administration to peak effects. Furthermore, we showed that baseline connectivity is associated with the extent of psilocybin-induced changes in functional connectivity. Lastly, psilocybin-induced changes correlated in a time-dependent manner with spatial gene expression patterns of the 5-HT2A (5-hydroxytryptamine 2A) and 5-HT1A (5-hydroxytryptamine 1A) receptors. CONCLUSIONS: These results suggest that the integration of functional connectivity in sensory regions and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.
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